Local Anesthetics Flashcards
Mechanism of Action
targets sodium channels –> prevents activation and inhibits sodium influx –> no action potential –> no impulse propagation
- uncharged form penetrates membrane, then turns into charged form and then binds channel
Na-K ATPase pump effects
generates 60-70 mV resting membrane potential
- leaky to K+
- accumulates (-) intracellular
Sodium Channel States
Resting = ready for an AP Open = after an AP has propagated and ions flowing through Inactive = not open but unable to propagate another AP
Local Anesthetic charges
LA = uncharged base
- able to penetrate the membrane
LAH+ = protonated quaternary amine
- responsible for binding, but when charged it is VERY hydrophilic and cannot penetrate the membrane
Preference for channel states and LA binding
Repeated depolarization = facilitates more effective binding
- bind open and inactive states
- LA cannot bind the resting state channel
Proportion of charged/uncharged
Proportion is a function of the pKa and environment pH
- pKa = pH - log[base]/[conjugate acid]
Lower pKa = greater % unionized (faster onset)
Higher pKa = greater % ionized (slower onset)
Differential Blockade
increased nerve fiber diameter
- this correlates to lower affinity for blockade
*BUT Myelinated fibers trump unmyelinated regardless of size
Type A fibers (Myelinated)
alpha = 12-20 nm --> proprioception beta = 5-15 nm --> touch, pressure delta = 2-5 nm --> pain and temp
Type B fibers (Myelinated)
3 nm –> preganglionic autonomic
Type C fibers (Unmyelinated)
0.3 - 1.5 nm –> dull pain, temp, touch
Structure of LA
Lipophilic group separated from hydrophilic group by an ester or an amide
@ physiologic pH –> local anesthetics are weak bases
Potency of LA
correlates with the octanol solubility
- reflects the ability of a drug to permeate the lipid membrane
Esters
Procaine
Chloroprocaine
Tetracaine
Amides
Lidocaine Mepivacaine Prilocaine Bupivacaine Ropivacaine
Procaine
pKa = 8.9 Potency = 1 Duration = 45-60 minutes
Chloroprocaine
pKa = 8.7 Potency = 2 Duration = 30-60 min
Tetracaine
pKa = 8.5 Potency = 8 Duration = 45-60 min
Lidocaine
pKa = 7.9 Potency = 2 Duration = 60-120 min
Mepivacaine
pKa = 7.6 Potency = 2 Duration = 90-180 min
Prilocaine
pKa = 7.9 Potency = 2 Duration = 60-120 min
Bupivacaine
pKa = 8.1 Potency = 8 Duration = 240-480 min
Ropivacaine
pKa = 8.1 Potency = 6 Duration = 240-480 min
Metabolism of LA
Esters = hydrolysis in plasma
- less likely for toxicity
Amides = hepatic microsomal enzymes
Absorption
IV > tracheal > intercostals > epidural > brachial plexus > subq
*absorption is much less with vasoconstrictor
